7 research outputs found
Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
- Author
- Aldrich M.C. (Melinda)
- Artigas M.S.
- Aschard H. (Hugues)
- Barr R.G. (Graham)
- Bentley A.R. (Amy)
- Boezen H.M. (Marike)
- Brusselle G.G. (Guy)
- Burkart K.M. (Kristin)
- Cassano P.A. (Patricia)
- Chen T.H.
- Couper D.J. (David)
- Curjuric I. (Ivan)
- Dupuis J. (Josée)
- Eijgelsheim M. (Mark)
- Eiriksdottir G. (Gudny)
- Elliott P. (Paul)
- Fornage M. (Myriam)
- Franceschini N. (Nora)
- Gharib S.A. (Sina)
- Gläser S. (Sven)
- Gu X. (Xiangjun)
- Gudnason V. (Vilmundur)
- Hall I.P. (Ian)
- Hammond C.J. (Christopher)
- Hancock D.B. (Dana)
- Harris T.B. (Tamara)
- Hartikainen A.L.
- Heckbert S.R. (Susan)
- Heinrich J. (Joachim)
- Henry A. (Amanda)
- Hofman A. (Albert)
- Homuth G. (Georg)
- Hysi P.G. (Pirro)
- Imboden M. (Medea)
- Janson C. (Christer)
- Jarvelin M.-R. (Marjo-Riitta)
- Jarvis D.L. (Deborah)
- Joubert B.R. (Bonnie)
- Khaw K-T. (Kay-Tee)
- Koch B. (Beate)
- Kraft P. (Peter)
- Kritchevsky S.B. (Stephen)
- Launer L.J. (Lenore)
- Laurie C.C. (Cathy)
- Liu J. (Jason)
- Liu Y. (YongMei)
- Loehr L.R. (Laura)
- Lohman K. (Kurt)
- London S.J. (Stephanie)
- Loos R.J.F. (Ruth)
- Loth D.W. (Daan)
- Lumley T. (Thomas)
- Manichaikul A. (Ani)
- Manning A.K. (Alisa)
- Marchini J. (Jonathan)
- Marciante K. (Kristin)
- McArdle W.L. (Wendy)
- Meibohm B. (Bernd)
- Mirel D. (Daniel)
- Morrison A.C. (Alanna)
- North K.E. (Kari)
- O'Connor G.T. (George)
- Obeidat M. (Ma'en)
- Postma D.S. (Dirkje)
- Probst-Hensch N.M. (Nicole M.)
- Psaty B.M. (Bruce)
- Ramasamy A. (Adaikalavan)
- Rich S.S. (Stephen)
- Rivadeneira Ramirez F. (Fernando)
- Rochat T. (Thierry)
- Rotter J.I. (Jerome)
- Smith A.V. (Davey)
- Smolonska J. (Joanna)
- Sood A. (Akshay)
- Spector T.D. (Timothy)
- Strachan D.P. (David)
- Stricker B.H.Ch. (Bruno)
- Tang W. (Wenbo)
- Tobin M.D. (Martin)
- Uitterlinden A.G. (André)
- Vonk J.M. (Judith)
- Völzke H. (Henry)
- Wain L.V. (Louise)
- Wareham N.J. (Nick)
- Wijmenga C. (Cisca)
- Wilk J.B. (Jemma)
- Williams O.D. (Dale)
- Wjst M. (Matthias)
- Zhai G. (Guangju)
- Zhao J.H. (Jing Hua)
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/12/2012
- Field of study
Abdominal Aortic Aneurysm Is Associated with a Variant in Low-Density Lipoprotein Receptor-Related Protein 1
- Author
- Abecasis G.R. (Gonçalo R.)
- Abecasis Gonçalo
- Absher D. (Devin)
- Adrienne Cupples L.
- Aherrahrou Zouhair
- Allayee Hooman
- Allione Alessandra
- Altshuler David
- Altshuler David
- Altshuler David
- Amin Najaf
- Anand Sonia
- Andersen Karl
- Anderson J.L. (Jeffrey L.)
- Angelica Merlini Pier
- Ardissino Diego
- Ardlie Kristin
- Assimes T.L. (Themistocles L.)
- Assimes Themistocles
- Aulchenko Yurii
- Baas Annette
- Badger Jonathan
- Balkau Beverley
- Ball Stephen
- Balmforth Anthony
- Bandinelli Stefania
- Barbalic maja
- Barnes Timothy
- Barroso Inês
- Barroso Inês
- Becker Diane
- Becker Lewis
- Beckmann Jacques
- Benediktsson Rafn
- Bengtsson Boström Kristina
- Bennett Amanda
- Berger Klaus
- Berglund G.
- Bergman R.N. (Richard N.)
- Bergman Richard N.
- Bergmann S. (Sven)
- Bingham Sheila
- Bis Joshua
- Blagieva Roza
- Blair R.D. (Ross D.)
- Blankenberg Stefan
- Blankensteijn Jan
- Bochud Murielle
- Bockxmeer Frank
- Boehm Bernhard
- Boehnke Michael
- Boehnke Michael
- Boekholdt Matthijs
- Boerwinkle E. (Eric)
- Boerwinkle Eric
- Bonnycastle L.L. (Lori L.)
- Bonnycastle Lori
- Bots Michiel
- Bown N.
- Bradley Declan
- Bragi Walters G.
- Braund Peter
- Bravenboer Bert
- Brown M.J. (Morris J.)
- Brown Morris
- Bumpstead Suzannah
- Bumpstead Suzannah
- Burnand Kevin
- Burton Paul
- Burtt Noël
- Buysschaert Ian
- Cambien François
- Campbell Harry
- Carlquist John
- Cauchi Stephane
- Caulfield Mark
- Chambers John
- Charpentier Guillaume
- Chen L. (Li)
- Child Anne
- Chines Peter
- Cichon Sven
- Clarke Robert
- Clough Rachel
- Cockerill Gillian
- Codd Veryan
- Coin L. (Lachlan)
- Collins F.S. (Francis S.)
- Collins Francis
- Connell John
- Cornelis Marilyn
- Couper David
- Crawford G.J. (Gabriel J.)
- Crawford Gabe
- Daly Mark
- Dam Rob
- Davies Robert
- de Jong P.E. (Paul E.)
- Dedoussis George
- Dehghan Abbas
- Deloukas P. (Panos)
- Deloukas P. (Panos)
- Deloukas Panagiotis
- Demissie Serkalem
- Devaney Joseph
- Di Gregorio Alessandra
- Diemert Patrick
- Dina Christian
- Do Ron
- Doering Angela
- Dominiczak Anna
- Doney Alex
- Duijn Cornelia
- Dupuis Josée
- Döring Angela
- Dörr Marcus
- Edkins Ted
- Eifert Sandra
- El Mokhtari Nour Eddine
- Elliott Amanda
- Elliott K.S. (Katherine S.)
- Elliott Katherine
- Elliott P. (Paul)
- Ellis Stephen
- Elosua R. (Roberto)
- Elosua Roberto
- Engert J.C. (James C.)
- Epstein Stephen
- Erdmann Jeanette
- Erdos Michael
- Eriksson Per
- Ernst F. (Florian)
- Eyheramendy Susana
- Faire Ulf
- Farrall Martin
- Felix Stephan
- Ferreira Teresa
- Ferrucci Luigi
- Fischer M. (Marcus)
- Florez J.C. (Jose C.)
- Folkersen Lasse
- Folsom Aaron
- Forouhi Nita
- Fox Caroline
- Franco-Cereceda Anders
- Franklin Christopher
- Frayling Timothy
- Freimer Nelson B.
- Freyer Jennifer
- Frikke-Schmidt Ruth
- Froguel Philippe
- Futers Simon
- Galan Pilar
- Ganser Martha
- Gateva Vesela
- Gerry Hill B.
- Gieger C. (Christian)
- Gieger C. (Christian)
- Gieger Christian
- Gigante Bruna
- Gilst Wiek
- Girelli Domenico
- Gloyn Anna
- Goel A. (Anuj)
- Golledge Jonathan
- Goodall Alison
- Graaf Jacqueline
- Grallert Harald
- Grarup Niels
- Green T. (Todd)
- Gretarsdottir S. (Solveig)
- Gretarsdottir Solveig
- Griffin Simon
- Grobbee Diederick
- Groop Leif
- Groop Leif
- Groves Christopher
- Guarrera Simonetta
- Gudnason Vilmundur
- Guiducci Candace
- Gulcher Jeffrey
- Gut Ivo
- Gwilliam Rhian
- Gyllensten U. (Ulf)
- Hadjadj Samy
- Hadley D. (David)
- Haeften Timon
- Hafez Hany
- Hall Alistair
- Halperin Eran
- Hammond Naomi
- Hamsten Anders
- Hansen T. (Torben)
- Harrison Seamus
- Harst Pim
- Hartikainen A.L.
- Hassanali Neelam
- Hattersley Andrew
- Hazen Stanley
- Heath Simon
- Hengstenberg Christian
- Hercberg Serge
- Herder Christian
- Herpt Thijs
- Hide Winston
- Hill A.A. (Andrew A.)
- Hitman Graham
- Hoek Mandy
- Hofman A. (Albert)
- Hofman Albert
- Hofmann Oliver
- Holm Hilma
- Homuth Georg
- Horne Benjamin
- Hu Frank
- Hua Zhao J. (Jing)
- Hughes Anne
- Humphries Steve
- Hunt Sarah
- Hunter D.J. (David J.)
- Huth Cornelia
- Hveem Kristian
- Illig Thomas
- Illig Thomas
- Illig Thomas
- Iribarren Carlos
- Isomaa Bo
- Jackson Anne
- Jackson Anne
- Jarvelin Marjo-Riitta
- Johnson A. (Anne)
- Johnson P.R.V. (Paul R. V.)
- Johnson Toby
- Jones G.T. (Gregory T.)
- Jones Gregory
- Jorgensen Torben
- Jousilahti Pekka
- Jukema Jan Wouter
- Kaiser Michael
- Kao Wen
- Kaplan Lee
- Kastelein John
- Kathiresan S. (Sekar)
- Kathiresan S. (Sekar)
- Khaw K.T.
- Khaw Kay-Tee
- Kiemeney Bart
- Klopp Norman
- Knowles Joshua
- Kolovou G. (Genovefa)
- Kong Augustine
- Kong Augustine
- Kooner Jaspal S.
- Kraft Peter
- Kuusisto Johanna
- König Inke
- Laakso M. (Markku)
- Laakso Markku
- Laaksonen Reijo
- Laan Maris
- Lakatta Edward
- Lambrechts Diether
- Langenberg Claudia
- Lathrop Mark
- Lauritzen Torsten
- Leander Karin
- Lettre Guillaume
- Lewis David
- Li Man
- Li X.
- Lieb Wolfgang
- Lieverse Aloysius
- Lim Noha
- Lindgren Cecilia
- Lindholt Jes
- Loley Christina
- Loos Ruth
- Lorbeer Roberto
- Lotery Andrew
- Lourdes Sampietro M.
- Luan J.
- Luben Robert
- Lucas G. (Gavin)
- Lyssenko Valeriya
- Mannucci Pier
- Maouche Seraya
- Marre Michel
- Marrugat Jaume
- Martinelli Nicola
- Matthiasson S.E. (Stefan E.)
- Matullo G.
- McArdle Wendy
- McCarroll Steve
- McCarthy Mark
- McCarthy Mark I.
- McCulloch Laura
- McKeown Pascal
- McNoe Les
- McPherson R. (Ruth)
- McPherson Ruth
- Meigs James
- Meisinger Christa
- Meitinger T. (Thomas)
- Meitinger T. (Thomas)
- Meitinger Thomas
- Melander O. (Olle)
- Melander Olle
- Meneton Pierre
- Merriman T.R. (Tony R.)
- Midthjell Kristian
- Mohlke Karen
- Mohlke Karen L.
- Mooser V. (Vincent)
- Mooser Vincent
- Morgan Thomas
- Morken M.A. (Mario A.)
- Morken Mario
- Morris Andrew
- Morris Andrew
- Muhlestein Joseph
- Munroe Patricia
- Munzel Thomas
- Musunuru Kiran
- März Winfried
- Mühleisen Thomas
- Nahrstaedt Janja
- Naik D.K. (Dilip K.)
- Najjar Samer
- Narisu Narisu
- Navarro Pau
- Navis Gerjan
- Nelson Christopher P.
- Newhouse Stephen
- Newton-Cheh Christopher
- Nilsson P. (Peter)
- Nilsson P. (Peter)
- Norman Paul E.
- Numans Mattijs
- Nöthen Markus
- O'Donnell Christopher
- O'Donnell Christopher J.
- O'Reilly Paul
- Olivieri O. (Oliviero)
- Onland-Moret N.C. (N. Charlotte)
- Org Elin
- Orho-Melander Marju
- Ouwehand Willem
- Owen Katharine
- Palmen Jutta
- Palmer Colin
- Panico Salvatore
- Pankow James
- Papadakis K. (Konstantinos)
- Patel Riyaz
- Patterson Chris
- Payne Felicity
- Peden John
- Pedersen Oluf
- Peltonen Leena Johanna
- Perola Markus
- Perry John
- Peters Annette
- Petersen A.K.
- Peyvandi Flora
- Pfeufer Arne
- Platou Carl
- Polidoro Silvia
- Potter Simon
- Pouta Anneli
- Powell Janet
- Pramstaller Peter Paul
- Preuss Michael
- Proença Christine
- Prokopenko Inga
- Qi Lu
- Qu Liming
- Quertermous Thomas
- Quyyumi Arshed
- Rader Daniel
- Rallidis Loukianos
- Rathmann Wolfgang
- Raychaudhuri Soumya
- Rayner Nigel William
- Reffelmann Thorsten
- Refstrup Mette
- Reilly M.P. (Muredach P.)
- Rettig Rainer
- Ricceri Fulvio
- Rice Catherine
- Rij Andre
- Roberts Robert
- Robertson Neil
- Rocheleau Ghislain
- Roden Michael
- Romanazzi Valeria
- Rosendaal Frits
- Rubin Diana
- Rudan Igor
- Sacerdote Carlotta
- Salomaa Veikko
- Salomaa Veikko
- Samani N.J. (Nilesh J.)
- Samani Nilesh
- Samani Nilesh
- Sampson M.J. (Michael J.)
- Sandhu Manjinder
- Sandhu Manjinder
- Sanna Serena
- Saxena Richa
- Sayers Ian
- Schadt Eric
- Scheet Paul
- Schillert Arne
- Schlessinger D. (David)
- Schouw Yvonne
- Schreiber S. (Stefan)
- Schrezenmeir J. (Jürgen)
- Schunkert Heribert
- Schwartz S.M. (Stephen M.)
- Schwartz S.M. (Stephen M.)
- Schäfer A. (Arne)
- Scott D Julian
- Scott L.J. (Laura J.)
- Scott Laura
- Scuteri Angelo
- Seedorf U. (Udo)
- Segrè Ayellet
- Shields Beverley
- Shrader Peter
- Sigurdsson G. (Gunnar)
- Sijbrands Eric
- Siscovick D.S. (David S.)
- Siscovick David
- Sivananthan Mohan
- Sivapalaratnam Suthesh
- Sladek Rob
- Smith A. (Alberto)
- Smith A.J.P.
- Smith Albert Vernon
- Smith T.B. (Tamara B.)
- Snieder Harold
- Snoep Jaapjan
- Sohrabi Soroush
- Song Kijoung
- Soranzo N. (Nicole)
- Soranzo Nicole
- Sparsø Thomas
- Spector Timothy
- Spertus John
- Stark K. (Klaus)
- Stefansson K. (Kari)
- Stefansson K. (Kari)
- Stein Lincoln
- Steinthorsdottir Valgerdur
- Stewart Alexandre F.
- Stirrups Kathy
- Stoll Monika
- Strachan David
- Strassburger Klaus
- Stringham H.M. (Heather M.)
- Stringham Heather
- Subirana Isaac
- Sun Qi
- Susan Burnett Mary
- Swift Amy
- Sylvius Nicolas
- Syvänen A.C.
- Tanaka Toshiko
- Tang W.
- Teijink J. A W
- Tennstedt Stephanie
- Teumer Alexander
- Thompson John
- Thompson John
- Thompson Matthew
- Thomson I.A. (Ian A.)
- Thorand Barbara
- Thorgeirsson Gudmundur
- Thorleifsson G. (Gudmar)
- Thorleifsson G. (Gudmar)
- Thorleifsson Gudmar
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir Unnur
- Tichet Jean
- Tobin Martin
- Tognoni G. (Giovanni)
- Tomaszewski Maciej
- Topless Ruth
- Tuomi Tiinamaija
- Tuomilehto Jaakko
- Tuomilehto Jaakko
- Tybjaerg-Hansen A.
- Uda Manuela
- Uiterwaal Cuno
- Uitterlinden A. (Andre)
- Uitterlinden André
- Valle T.T. (Timo T.)
- van Rij A. (Andre)
- Vasudevan Thodur
- Vicky Phillips L.
- Vineis Paolo
- Vliet-Ostaptchouk Jana
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin F.)
- Voight Benjamin
- Vollenweider Peter
- Völker Uwe
- Völzke Henry
- Waeber Gérard
- Wain Louise
- Walker M. (Mark)
- Wallace Chris
- Waltham Matthew
- Wareham N.J. (Nicholas J.)
- Wareham Nick
- Wareham Nick
- Watanabe R.M. (Richard M.)
- Waterworth Dawn
- Watkins Hugh
- Webster J. (John)
- Weedon Michael
- Welch Ryan
- Wells George
- Wichmann H.E. (H. Erich)
- Wichmann Heinz Erich
- Wichmann Heinz Erich
- Wijmenga C. (Cisca)
- Wijmenga Cisca
- Wild John
- Wild Philipp
- Willenborg Christina
- Willer C.J. (Cristen J.)
- Willer Cristen
- Williams Frances
- Wilson J.F. (James F.)
- Witteman J. (Jacqueline)
- Witteman Jacqueline
- Wright Benjamin
- Wright Benjamin
- Wu Guanming
- Ye S. (Shu)
- Yu Grace
- Yuan Xin
- Zeggini Eleftheria
- Zeggini Eleftheria
- Zelenika Diana
- Zeller Tanja
- Zhai Guangju
- Zhang Feng
- Ziegler A. (Andreas)
- Zwart John-Anker
- Publication venue
- Elsevier
- Publication date
- 01/01/2011
- Field of study
Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10−5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10−5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10−10, odds ratio 1.15 [1.10–1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04–1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression
Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals
- Author
- Abecasis G.R. (Goncalo R.)
- Abecasis G.R. (Goncalo R.)
- Abecasis G.R. (Gonçalo R.)
- Abecasis G.R. (Gonçalo)
- Adair L.S. (Linda)
- Allison M.A. (Matthew)
- Altshuler D. (David)
- Altshuler D. (David)
- Amin N. (Najaf)
- An P. (Ping)
- Ardlie K.G. (Kristin)
- Ardlie K.G. (Kristin)
- Ariyurek Y. (Yavuz)
- Aulchenko Y.S. (Yurii S.)
- Aulchenko Y.S. (Yurii S.)
- Aulchenko Y.S. (Yurii)
- Bacquer O.L. (Olivier)
- Balkau B. (Beverley)
- Balkau B. (Beverley)
- Ballantyne C. (Christie)
- Ballantyne C.M. (Christie M.)
- Ballantyne C.M. (Christie M.)
- Bandinelli S. (Stefania)
- Bandinelli S. (Stefania)
- Barbalic M. (maja)
- Barroso I.
- Barroso I.E. (Inês)
- Barroso I.E. (Inês)
- Barter P. (Phil)
- Beekman M. (Marian)
- Beilby J.P. (John)
- Ben-Shlomo Y.
- Benediktsson R. (Rafn)
- Benediktsson R. (Rafn)
- Bennett A.J. (Amanda)
- Bennett A.J. (Amanda)
- Bergman R.N. (Richard N.)
- Bergman R.N. (Richard N.)
- Bergman R.N. (Richard N.)
- Bergmann S.M. (Sven)
- Bidulescu A. (Aurelian)
- Bis J.C. (Joshua)
- Blagieva R. (Roza)
- Bochud M. (Murielle)
- Boehm B.O. (Bernhard)
- Boehnke M. (Michael)
- Boehnke M. (Michael)
- Boehnke M. (Michael)
- Boekholdt S.M. (Matthijs)
- Boerwinkle E. (Eric)
- Boerwinkle E. (Eric)
- Boerwinkle E.A. (Eric)
- Bonnefond A. (Amélie)
- Bonnycastle L.L. (Lori L.)
- Bonnycastle L.L. (Lori L.)
- Bonnycastle L.L. (Lori)
- Boomsma D.I. (Dorret I)
- Boomsma D.I. (Dorret I.)
- Boomsma D.I. (Dorret)
- Borch-Johnsen K.
- Borecki I.B. (Ingrid B)
- Borja J.B. (Judith)
- Boström K.B. (Kristina Bengtsson)
- Bouatia-Naji N. (Nabila)
- Bravenboer B. (Bert)
- Brunner E. (Eric)
- Buchanan T.A. (Thomas)
- Bumpstead S. (Suzannah)
- Bumpstead S. (Suzannah)
- Burtt N.P. (Noël P.)
- Burtt N.P. (Noël)
- Buxbaum S.G. (Sarah)
- Böhringer S. (Stefan)
- Böttcher Y. (Yvonne)
- Campbell H. (Harry)
- Campbell H. (Harry)
- Campbell H. (Harry)
- Cao A. (Antonio)
- Carlson O.D. (Olga)
- Cauchi S. (Stephane)
- Caulfield M. (Mark)
- Caulfield M.J. (Mark J.)
- Cavalcanti-Proença C. (Christine)
- Chambers J. (John)
- Chambers J.C. (John C.)
- Charpentier G. (Guillaume)
- Charpentier G. (Guillaume)
- Chasman D.I. (Daniel)
- Chen I. (Ida)
- Chen Y.-D.I. (Yii-Der Ida)
- Chen Y.D.I. (Yii-Der Ida)
- Chines P.S. (Peter S.)
- Chines P.S. (Peter)
- Cho Y.S. (Yoon Shin)
- Clarke R. (Robert)
- Coassin S. (Stefan)
- Coin L. (Lachlan)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis)
- Cooper C. (Charles)
- Cooper C. (Cyrus)
- Cooper M.N. (Matthew)
- Cornelis M. (Marilyn)
- Cornelis M. (Marilyn)
- Couper D.J. (David J.)
- Couper D.J. (David)
- Crawford G. (Gabe)
- Crawford G. (Gabe)
- Crawford G. (Gabriel)
- Crisponi L. (Laura)
- Croteau-Chonka D.C. (Damien)
- Daly M.J. (Mark)
- Dam R.M. (Rob) van
- Dastani Z. (Zari)
- Day I.N.M. (Ian)
- Dedoussis G.V. (George)
- Dehghan A. (Abbas)
- Deloukas P. (Panagiotis)
- Deloukas P. (Panagiotis)
- Delplanque J. (Jerome)
- DIAGRAM+ Consortium
- Dina C. (Christian)
- Dina C. (Christian)
- Dominiczak A. (Anna)
- Dominiczak A.F. (Anna F.)
- Doney A.S.F. (Alex S. F.)
- Doney A.S.F. (Alex)
- Duijn C.M. (Cornelia) van
- Duncan B.B. (Bruce)
- Dupuis J. (Josée)
- Dupuis J. (Josée)
- Dupuis J. (Josée)
- Döring A. (Angela)
- Ebrahim S. (Shanil)
- Egan J.M. (Josephine)
- Egan J.M. (Josephine)
- Ejebe K.G. (Kenechi)
- Elliott A.L. (Amanda)
- Elliott A.L. (Amanda)
- Elliott K.S. (Katherine)
- Elliott P. (Paul)
- Erdmann J. (Jeanette)
- Erdmann J. (Jeanette)
- Erdos M.R. (Michael)
- Erdos M.R. (Michael)
- Evans D.M. (David)
- Faire U. (Ulf) de
- Fedson A.C. (Annette)
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- Thorsteinsdottir U. (Unnur)
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- Tichet J. (Jean)
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- Timpson N.J. (Nicholas J.)
- Timpson N.J. (Nicholas)
- Tracy R.P. (Russell)
- Tuomi T. (Tiinamaija)
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- Tuomilehto J. (Jaakko)
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- Tuomilehto J. (Jaakko)
- Tönjes A. (Anke)
- Uda M. (Manuela)
- Uda M. (Manuela)
- Uh H.-W. (Hae-Won)
- Uitterlinden A. (Andre)
- Uitterlinden A.G. (Andre G.)
- Uitterlinden A.G. (André)
- Valle T.T. (Timo T.)
- van Duijn C. (Cornelia)
- van Duijn C.M. (Cornelia M.)
- van Duijn C.M. (Cornelia M.)
- van Hoek M. (Mandy)
- Varma D. (Dhiraj)
- Viikari J. (Jorma)
- Visvikis-Siest S. (Sophie)
- Vitart V. (Veronique)
- Vitart V. (Veronique)
- Vliet-Ostaptchouk J.V. (Jana) van
- Vogelzangs N. (Nicole)
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin)
- Vollenweider P. (Peter)
- Vollenweider P. (Peter)
- Vollenweider P. (Peter)
- Waeber G. (Gérard)
- Waeber G. (Gérard)
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- Walker M. (Mark)
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- Ward K.L. (Kim L.)
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- Watanabe R.M. (Richard M.)
- Watanabe R.M. (Richard)
- Waterworth D. (Dawn)
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- Waterworth D.M. (Dawn)
- Watkins H. (Hugh)
- Weedon M.N. (Michael)
- Weedon M.N. (Michael)
- Welch R.P. (Ryan)
- Wheeler E. (Eleanor)
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- Wichmann H.-E. (H.-Erich)
- Wichmann H.E. (H. Erich)
- Wichmann H.E. (Heinz Erich)
- Wichmann H.E. (Heinz Erich)
- Wijmenga C. (Cisca)
- Wild S.H. (Sarah)
- Willems van Dijk J.A.P. (Ko)
- Willems S.M. (Sara)
- Willems-vanDijk K. (Ko)
- Willemsen G.
- Willemsen G.A.H.M. (Gonneke)
- Willer C.J. (Cristen J.)
- Willer C.J. (Cristen)
- Williams G.H. (Gordon)
- Wilson J.F. (James F.)
- Wilson J.F. (James)
- Wilson J.G. (James G.)
- Winkler T.W. (Thomas W.)
- Witteman J. (Jacqueline)
- Witteman J.C.M. (Jacqueline C. M.)
- Witteman J.C.M. (Jacqueline)
- Witteman J.C.M. (Jaqueline C. M.)
- Wong T.Y. (Tien Y.)
- Wood A.R. (Andrew)
- Wright A.F. (Alan)
- Wright A.F. (Alan)
- Wu G. (Guanming)
- Wu Y. (Ying)
- Yarnell J.W.G. (John W.)
- Yuan X. (Xin)
- Zabena C. (Carina)
- Zee R.Y.L. (Robert)
- Zeggini E. (Eleftheria)
- Zeggini E. (Eleftheria)
- Zelenika D. (Diana)
- Zethelius B. (Björn)
- Zhai G. (Guangju)
- Zhang W. (Weihua)
- Zhao J.H. (Jing Hua)
- Zhao J.H. (Jing Hua)
- Zhao J.H. (Jing Hua)
- Ziegler A. (Andreas)
- Zillikens M.C. (Carola)
- Zwart J-A. (John-Anker)
- Ódonnell C.J. (Christopher)
- Publication venue
- Publication date
- 01/01/2012
- Field of study
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance
Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes
- Author
- Abecasis G. (Goncalo)
- Abecasis G.R. (Gonçalo)
- Abecasis G.R. (Gonçalo)
- Aben K.K.H. (Katja)
- Absher D. (Devin)
- Absher D. (Devin)
- Aherrahrou Z. (Zouhair)
- Ahlqvist E. (Emma)
- Ahmadi K.R. (Kourosh)
- Ahmed N. (Nabeel)
- Alavere H. (Helene)
- Alibrandi M.T.S. (Maria)
- Allayee H. (Hooman)
- Allen H.L.
- Almgren P. (Peter)
- Altshuler D. (David)
- Amin N. (Najaf)
- Anand S.S. (Sonia)
- Andersen K.K. (Karl)
- Ardissino D. (Diego)
- Ardlie K.G. (Kristin)
- Armitage J. (Jane)
- Arnold A.M. (Alice)
- Aspelund T. (Thor)
- Assimes T.L. (Themistocles)
- Assmann G. (Gerd)
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- Azhar M. (Muhammad)
- Balkau B. (Beverley)
- Ball S.G. (Stephen G.)
- Barbalic M. (maja)
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- Barlassina C. (Christina)
- Barlera S. (Simona)
- Barnes D. (Daniel)
- Barnes T.A. (Timothy)
- Barrett A. (Angela)
- Barroso I.E. (Inês)
- Bataille V. (Veronique)
- Becker D.M. (Diane)
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- Travers M.E. (Mary)
- Tuomi T. (Tiinamaija)
- Tuomilehto J. (Jaakko)
- Turrini F. (Fabiola)
- Tyrer J.P. (Jonathan)
- Tönjes A. (Anke)
- Uda M. (Manuela)
- Uitterlinden A.G. (André)
- Valle T.T. (Timo T.)
- Van Dam R.M. (Rob M.)
- van't Hooft F. (Ferdinand)
- Van't Hooft F. (Ferdinand)
- Vatin V. (Vincent)
- Vedantam S. (Sailaja)
- Visscher P.M. (Peter M.)
- Visscher P.M. (Peter)
- Vitart V. (Veronique)
- Vliet-Ostaptchouk J.V. (Jana) van
- Voight B.F. (Benjamin)
- Wabitsch M. (Martin)
- Waeber G. (Gérard)
- Waite L. (Lindsay)
- Walker M. (Mark)
- Wallaschofski H. (Henri)
- Walters G.B. (Bragi)
- Wareham N.J. (Nicholas J.)
- Wareham N.J. (Nick)
- Watanabe R.M. (Richard)
- Watkins H. (Hugh)
- Weedon M.N. (Michael)
- Weedon M.N. (Michael)
- Welch R. (Ryan)
- Welch R.P. (Ryan)
- Wells G.A. (George)
- Weyant R.J. (Robert)
- Wheeler E. (Eleanor)
- White C.C. (Charles)
- Wichmann H.-E. (H-Erich)
- Wichmann H.E. (Heinz Erich)
- Widen E. (Elisabeth)
- Wiegand S. (Susanna)
- Wijmenga C. (Cisca)
- Wiklund F. (Fredrik)
- Wild P.S. (Philipp)
- Wild S.H. (Sarah)
- Wilk A. (Alicja)
- Willemsen G.A.H.M. (Gonneke)
- Willenborg C. (Christina)
- Willer C.J. (Cristen)
- Wilson J.F. (James F.)
- Wingerden S. (Sophie) van
- Winkler T.W. (Thomas W.)
- Witte D.R. (Daniel R.)
- Witte D.R. (Deniel)
- Witteman J. (Jacqueline)
- Witteman J.C.M. (Jacqueline)
- Witteman J.C.M. (Jaqueline C.M.)
- Wood A.R. (Andrew)
- Workalemahu T. (Tsegaselassie)
- Wright A.F. (Alan)
- Wright B.J. (Benjamin)
- Wu G. (Guanming)
- Xie W. (Weijia)
- Xu J. (Jianfeng)
- Yang J. (Jian)
- Yang J. (Joanna)
- Yang T.-P. (Tsun-Po)
- Ye S. (Shu)
- Zabena C. (Carina)
- Zaidi M.A. (Aghar)
- Zaman K.S. (Khan Shah)
- Zeggini E. (Eleftheria)
- Zeller T. (Tanja)
- Zethelius B. (Björn)
- Zgaga L. (Lina)
- Zhang Q. (Qunyuan)
- Zhang W. (Weihua)
- Zhao J.H. (Jing Hua)
- Ziegler A. (Andreas)
- Ziegler A. (Andreas)
- Zillikens M.C. (Carola)
- Zitting P. (Paavo)
- Zondervan K.T. (Krina T.)
- Zondervan K.T. (Krina)
- Zwart J-A. (John-Anker)
- Öhrvik J. (John)
- Östenson C.-G. (Claes-Göran)
- Publication venue
- Publication date
- 01/10/2011
- Field of study
OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10-8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/ C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 3 10-4), improved b-cell function (P = 1.1 × 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10-6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS - We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
- Author
- Adams H.H.H. (Hieab)
- Ago T. (Tetsuro)
- Almgren P. (Peter)
- Amouyel P. (Philippe)
- Amouyel P. (Philippe)
- Anderson C.D. (Christopher D.)
- Anugu P. (Pramod)
- Ay H. (Hakan)
- Bakker P.I.W. (Paul) de
- Baldassarre D. (Damiano)
- Bartz T.M. (Traci M.)
- Benavente O.R. (Oscar R.)
- Beutner F. (Frank)
- Bevan S. (Steve)
- Bis J.C. (Joshua)
- Björkegren J.L.M. (Johan L.M.)
- Boerwinkle E.A. (Eric)
- Boncoraglio G. (Giorgio Battista)
- Bowden D.W. (Donald)
- Britton A.R.
- Brown R.D. (Robert D.)
- Burkhardt R. (Ralph)
- Butterworth A.S. (Adam S.)
- Campbell H. (Harry)
- Carrera C. (Caty)
- Carty C.L. (Cara L.)
- Casas J.P. (Juan)
- Chambers J.C. (John C.)
- Chasman D.I. (Daniel)
- Chauhan G. (Ganesh)
- Chen W-M.
- Chong M. (Michael)
- Christophersen I.E. (Ingrid E.)
- Civelek M. (Mete)
- Codoni V. (Veronica)
- Cole J.W. (John W.)
- Correa D.D.
- Cotlarciuc I. (Ioana)
- Cox A.J. (Amanda J.)
- Cruchaga C. (Carlos)
- Dale C. (Caroline)
- Danesh J. (John)
- Deanfield J. (John)
- Deary I.J. (Ian)
- Debette S. (Stéphanie)
- Dehghan A. (Abbas)
- DeStefano A.L. (Anita)
- Dhana K. (Klodian)
- Duan Q. (Qing)
- Duijn C.M. (Cornelia) van
- Dörr M. (Marcus)
- Ellinor P.T. (Patrick)
- Elliott P. (Paul)
- Engelter S.T. (Stefan)
- Engmann J. (Jorgen)
- Evans M.K. (Michele)
- Faire U. (Ulf) de
- Falcone G.J. (Guido J.)
- Fava C. (Cristiano)
- Fernandez-Cadenas I. (Israel)
- Finan C. (Chris)
- Franceschini N. (Nora)
- Franco O.H. (Oscar)
- Franzén O. (Oscar)
- Galesloot T.E. (Tessel)
- Gertow K. (Karl)
- Giambartolomei C. (Claudia)
- Giese A.-K. (Anne-Katrin)
- Giral P. (Philippe)
- Gottesman R.F. (Rebecca)
- Graaf J. (Jacqueline) de
- Graff M. (Misa)
- Gretarsdottir S. (Solveig)
- Grewal R.P. (Raji P.)
- Grossi E. (Enzo)
- Gudnason V. (Vilmundur)
- Guo X. (Xiuqing)
- Gustafsson S. (Stefan)
- Haessler J. (Jeff)
- Halcox J. (Julian)
- Hamsten A. (Anders)
- Hardy R. (Rebecca)
- Harris T.B. (Tamara B.)
- Harris T.B. (Tamara)
- Harst P. (Pim) van der
- Hassan A. (Ahamad)
- Hata J. (Jun)
- Havulinna A.S. (Aki)
- He J. (Jiang)
- Heckbert S.R. (Susan)
- Hedblad B. (Bo)
- Heiss G. (Gerardo)
- Hingorani A. (Aroon)
- Hoed M. (Marcel) den
- Hofer E. (Edith)
- Hofman A. (Albert)
- Holdt L.M. (Lesca)
- Holliday E.G. (Elizabeth)
- Hopewell J.
- Howard G. (George)
- Howson J.M.M. (Joanna M. M.)
- Hsu F.-C. (Fang-Chi)
- Humphries S.E. (Steve)
- Huntley R.P. (Rachael P.)
- Hwang S.-J. (Shih-Jen)
- Hyacinth H.I. (Hyacinth I.)
- Hägg S. (Sara)
- Ikram M.A. (Arfan)
- Ingelsson E. (Erik)
- Irvin M.R. (Marguerite R.)
- Isaacs A.J. (Aaron)
- Jern C. (Christina)
- Jian X. (Xueqiu)
- Jimenez-Conde J. (Jordi)
- Johnson A.D. (Andrew)
- Johnson J.A. (Julie A.)
- Joshi P.K. (Peter)
- Jukema J.W. (J. Wouter)
- Jukema J.W. (Jan Wouter)
- Kamatani Y. (Yoichiro)
- Kanai M. (Masahiro)
- Kao W.H.L. (Wen)
- Kato N. (Norihiro)
- Kavousi M. (Maryam)
- Keene K.L. (Keith)
- Kiemeney L.A.L.M. (Lambertus A. L. M.)
- Kissela B.M. (Brett M.)
- Kittner T. (Thomas)
- Kivimaki M. (Mika)
- Kleindorfer D.O. (Dawn O.)
- Kooner J.S. (Jaspal S.)
- Kooperberg C. (Charles)
- Koplev S. (Simon)
- Kubisch C. (Christian)
- Kubo M. (Michiaki)
- Kuh D. (Diana)
- Kumari M. (Meena)
- Kurl S. (Sudhir)
- Lange L.A. (Leslie)
- Langefeld C.D. (Carl D.)
- Langefeld C.D. (Carl)
- Langenberg C. (Claudia)
- Launer L.J. (Lenore)
- Lawlor D.A. (Debbie)
- Lee J.-M. (Jin-Moo)
- Leeuwen E.M. (Elisa) van
- Lehtimäki T. (Terho)
- Lemmens R. (Robin)
- Lewis C.M. (Cathryn)
- Leys D. (Didier)
- Liang J. (Jingjing)
- Lin W.-Y. (Wei-Yu)
- Lindgren A.G. (Arne G.)
- Loeffler M. (Markus)
- Longstreth Jr W.T.
- Lorentzen E. (Erik)
- Lovering R.C. (Ruth C.)
- Lu L. (Lingyi)
- Lubitz S.A. (Steven A.)
- Lyytikäinen L.-P. (Leo-Pekka)
- Magnusson P.K. (Patrik)
- Maguire J.M. (Jane)
- Malik R. (Rainer)
- Manichaikul A. (Ani)
- Mannarino E. (Elmo)
- Marioni R.E. (Riccardo)
- Markus H.S. (Hugh)
- McArdle P.F. (Patrick)
- McLachlan S. (Stela)
- Melander O. (Olle)
- Melander O. (Olle)
- Meschia J.F. (James F.)
- Mishra A. (Aniket)
- Mook-Kanamori D.O. (Dennis O.)
- Morris R.W. (Richard)
- Morrison A.C. (Alanna)
- Mosley T.H. (Thomas H.)
- Muir K.W. (Keith)
- Musani S.K. (Solomon K.)
- Mutsert R. (Reneé) de
- Nalls M.A. (Michael)
- Newman A.B. (Anne B.)
- Ninomiya T. (Toshiharu)
- Nolte I.M. (Ilja)
- Noordam R. (Raymond)
- Okada Y. (Yukinori)
- O’Donnell M.J. (Martin J.)
- O’Leary D.H. (Daniel H.)
- Palmas W. (Walter)
- Pare G. (Guillame)
- Pasaniuc B. (Bogdan)
- Pastinen T. (Tomi)
- Penninx B.W.J.H. (Brenda)
- Pitkanen N. (Niina)
- Plagnol V. (Vincent)
- Post W.S. (Wendy S.)
- Pott J. (Janne)
- Price J. (Jacqueline)
- Psaty B.M. (Bruce)
- Pulit S.L. (Sara)
- Raffield L.M. (Laura M.)
- Raitakari O. (Olli)
- Rannikmäe K. (Kristiina)
- Rauramaa R. (Rainer)
- Reiner A.P. (Alexander P.)
- Rexrode K. (Kathryn)
- Rice K.M. (Kenneth)
- Rich S.S. (Stephen)
- Ridker P.M. (Paul)
- Ring S.M. (Susan)
- Rivadeneira Ramirez F. (Fernando)
- Rolfs A. (Arndt)
- Rosamond W.D. (Wayne)
- Rosand J. (Jonathan)
- Roselli C. (Carolina)
- Rost N.S. (Natalia)
- Rothwell P.M. (Peter)
- Rotter J.I. (Jerome I.)
- Roussos A. (Alexandra)
- Rueda-Ochoa O.L. (Oscar)
- Rundek T. (Tatjana)
- Rutten-Jacobs L. (Loes)
- Ruusalepp A. (Arno)
- Saba Y. (Yasaman)
- Sakaue S. (Saori)
- Sale M.M. (Michele M.)
- Saleheen D. (Danish)
- Salomaa V. (Veikko)
- Sanghera D.K. (Dharambir K.)
- Sapkota B.R. (Bishwa R.)
- Sargurupremraj M. (Muralidharan)
- Schadt E.E. (Eric E.)
- Schadt E.E. (Eric)
- Schmidt C.O. (Carsten O.)
- Schmidt H. (Helena)
- Schmidt R. (Reinhold)
- Schmidt R. (Reinhold)
- Schminke U. (Ulf)
- Schminke U. (Ulf)
- Scholz M. (Markus)
- Seldenrijk K.A. (Kees)
- Sennblad B. (Bengt)
- Seshadri S. (Sudha)
- Shah S. (Sonia)
- Shah T. (Tina)
- Sharma P. (Pankaj)
- Sitzer M. (Matthias)
- Slowik A. (Agnieszka)
- Smit A.J. (Andries)
- Smith A.V. (Albert)
- Smith N.L. (Nicholas)
- Snieder H. (Harold)
- Strawbridge R.J. (Rona)
- Strbian D. (Daniel)
- Sudlow C. (Cathie)
- Tai E.S. (E. Shyong)
- Tajuddin S.M. (Salman M.)
- Takeuchi F. (Fumihiko)
- Tanislav C. (Christian)
- Tatlisumak T. (Turgut)
- Taylor K.D. (Kent)
- Teumer A. (Alexander)
- Teupser D. (Daniel)
- Thiery J.P. (Joachim)
- Thijs V. (Vincent)
- Thorleifsson G. (Gudmar)
- Thorsteinsdottir U. (Unnur)
- Tiedt S. (Steffen)
- Traylor M. (Matthew)
- Tregouet D.-A. (David-Alexandre)
- Tremoli E. (Elena)
- Trompet S. (Stella)
- Trompet S. (Stella)
- Tzourio C. (Christophe)
- Uitterlinden A.G. (André)
- van der Laan S.W. (Sander W.)
- Veglia F. (Fabrizio)
- Vries P.S. (Paul) de
- Völker U. (Uwe)
- Völzke H. (Henry)
- Walters M. (Matthew)
- Wannamethee S.G. (Goya)
- Wardlaw J.M. (J.)
- Wareham N.J. (Nick)
- Wassel C.L. (Christina)
- Wassertheil-Smoller S. (Sylvia)
- Whincup P.H. (Peter)
- Wiggins K.L. (Kerri)
- Wilson J.F. (James F.)
- Wilson J.F. (James)
- Winkler T.W. (Thomas W.)
- Wong A. (Andrew)
- Wong Q. (Quenna)
- Woo D. (Daniel)
- Worrall B.B. (Bradford B.)
- Yang Q. (Qiong Fang)
- Yusuf S. (Salim)
- Zhang X. (Xiaoling)
- Zhu X. (Xiaofeng)
- Zonderman A.B.
- Zwart J-A. (John-Anker)
- Ódonnell C.J. (Christopher)
- Publication venue
- Nat Commun
- Publication date
- 01/01/2018
- Field of study
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans
Rare and low-frequency coding variants alter human adult height
- Author
- Abecasis G.R. (Gonçalo)
- Aben K.K.H. (Katja)
- Adair L.S. (Linda)
- Alam D.S. (Dewan S.)
- Albrecht E. (Eva)
- Allin K.H. (Kristine H)
- Allison M.A. (Matthew)
- Amouyel P. (Philippe)
- Angelantonio E. (Emanuele) di
- Appel E.V. (Emil V.)
- Arveiler D. (Dominique)
- Asselbergs F.W. (Folkert)
- Auer P. (Paul)
- Bakker P.I.W. (Paul) de
- Balkau B. (Beverley)
- Banas B. (Bernhard)
- Bang L.E. (Lia E.)
- Benn M. (Marianne)
- Bergmann S. (Sven)
- Bielak L.F. (Lawrence F.)
- Blüher M. (Matthias)
- Boehnke M. (Michael)
- Boeing H. (Heiner)
- Boerwinkle E.A. (Eric)
- Bonnycastle L.L. (Lori)
- Borecki I.B. (Ingrid)
- Bork-Jensen J. (Jette)
- Borst G.J. (Gert) de
- Bots M.L. (Michiel)
- Bottinger E.P. (Erwin)
- Bowden D.W. (Donald)
- Brandslund I. (Ivan)
- Breen G. (Gerome)
- Brilliant M.H. (Murray H.)
- Broer L. (Linda)
- Burt A.D. (Alastair)
- Butterworth A.S. (Adam)
- Böger C.A. (Carsten)
- Carey D.J. (David J.)
- Caulfield M. (Mark)
- Chambers J.C. (John)
- Chasman D.I. (Daniel)
- Chen Y.-D.I. (Yii-Der Ida)
- Chowdhury R. (Rajiv)
- Christensen C. (Cramer)
- Chu A.Y. (Audrey)
- Cocca M. (Massimiliano)
- Collins F.S. (Francis)
- Cook J.P. (James P.)
- Corley J. (Janie)
- Cox A.J. (Amanda J.)
- Cuellar-Partida G. (Gabriel)
- Danesh J. (John)
- Davies G. (Gail)
- De Denus S. (Simon)
- De Groot M.C.H. (Mark C.H.)
- Deary I.J. (Ian)
- Dedoussis G.V. (George)
- Deloukas P. (Panos)
- Demerath E.W. (Ellen)
- Dennis J. (Joe)
- Drenos F. (Fotios)
- Du M. (Mengmeng)
- Duijn C.M. (Cornelia) van
- Dunning A.M. (Alison M.)
- Easton D.F. (Douglas)
- Ebeling T. (Tapani)
- Edwards T.L. (Todd L.)
- Ellinor P.T. (Patrick)
- Elliott P. (Paul)
- Esko T. (Tõnu)
- Evangelou E. (Evangelos)
- Farmaki A.-E. (Aliki-Eleni)
- Faul J.D. (Jessica D.)
- Feitosa M.F. (Mary Furlan)
- Feng S. (Shuang)
- Ferrannini E. (Ele)
- Ferrario M.M. (Marco M.)
- Ferrieres J. (Jean)
- Fine R.S. (Rebecca S.)
- Florez J.C. (Jose)
- Ford I.
- Fornage M. (Myriam)
- Franks P.W. (Paul)
- Frayling T.M. (Timothy)
- Frikke-Schmidt R. (Ruth)
- Galbany J.C. (Jordi Corominas)
- Galesloot T.E. (Tessel)
- Gan W. (Wei)
- Gandin I. (Ilaria)
- Gasparini P. (Paolo)
- Giedraitis V. (Vilmantas)
- Giri A. (Ayush)
- Girotto S.
- Gordon S.D. (Scott D.)
- Gordon-Larsen P. (Penny)
- Gorski M. (Mathias)
- Graff M.J. (Maud J.L.)
- Grarup N. (Niels)
- Grove M.L. (Megan)
- Gudnason V. (Vilmundur)
- Guo X. (Xiuqing)
- Gustafsson S. (Stefan)
- Hansen T. (T.)
- Harris K.M. (Kathleen Mullan)
- Harris T.B. (Tamara)
- Hart't L.M. (Leen M.)
- Hattersley A.T. (Andrew)
- Hayward C. (Caroline)
- He L. (Liang)
- Heard-Costa N.L. (Nancy)
- Heid I.M. (Iris)
- Heikkilä K. (Kauko)
- Helgeland Ø. (Øyvind)
- Hernesniemi J. (Jussi)
- Hewit A.W. (Alex)
- Highland H. (Heather)
- Hirschhorn J.N. (Joel)
- Hocking L.J. (Lynne)
- Hollander A.I. (Anneke)
- Hollensted M. (Mette)
- Holmen O.L. (Oddgeir)
- Hovingh G.K. (Kees)
- Howson J.M.M. (Joanna M.M.)
- Hoyng C.B. (Carel)
- Huang P.L. (Paul L.)
- Hveem K. (Kristian)
- Ikram M.K. (Kamran)
- Ingelsson E. (Erik)
- Jackson A.U. (Anne)
- Jansson J.-H. (Jan-Håkan)
- Jarvik G.P. (Gail)
- Jensen G.B. (Gorm B.)
- Jhun M.A. (Min A.)
- Jia Y. (Yucheng)
- Jiang X. (Xuejuan)
- Johansson S. (Stefan)
- Jorgensen T. (Torben)
- Jousilahti P. (Pekka)
- Jukema J.W. (Jan Wouter)
- Justice A.E. (Anne)
- Jørgensen M.E. (Marit E.)
- Kahali B. (Bratati)
- Kahn R. (René)
- Kamstrup P.R. (Pia R.)
- Kanoni S. (Stavroula)
- Kao W.H.L. (Wen)
- Kaprio J. (Jaakko)
- Karaderi T. (Tugce)
- Karaleftheri M. (Maria)
- Kardia S.L.R. (Sharon L.R.)
- Karpe F. (Fredrik)
- Kathiresan S. (Sekar)
- Kee F. (Frank)
- Keeman J.N.
- Kiemeney L.A.L.M. (Bart)
- Kitajima H. (Hidetoshi)
- Kjaer T.R. (Troels R.)
- Kluivers K.B. (Kirsten B.)
- Kocher T.
- Komulainen P. (Pirjo)
- Kontto J. (Jukka)
- Kooner J.S. (Jaspal S.)
- Kooperberg C. (Charles)
- Kovacs P. (Peter)
- Kriebel J. (Jennifer)
- Kuivaniemi H. (Helena)
- Kutalik Z. (Zoltán)
- Kuusisto J. (Johanna)
- Kähönen M. (Mika)
- Küry S. (Sébastien)
- La Bianca M. (Martina)
- Laakso M. (Markku)
- Lakka T.A. (Timo)
- Lamparter D. (David)
- Lange E.M. (Ethan)
- Lange L.A. (Leslie)
- Langefeld C.D. (Carl)
- Langenberg C. (Claudia)
- Larson E.B. (Eric B.)
- Lee I.-T. (I-Te)
- Lehtimäki T. (Terho)
- Lettre G. (Guillaume)
- Lewis C.E. (Cora E.)
- Li H. (Huaixing)
- Li J. (Jin)
- Li-Gao R. (Ruifang)
- Lin H. (Honghuang)
- Lin L.-A. (Li-An)
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- Vestergaard H. (Henrik)
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- Vogt T.F. (Thomas F.)
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- Walker M. (Mark)
- Wang C.A. (Carol A.)
- Wang F. (Feijie)
- Wang S. (Shuai)
- Wang Y. (Yiqin)
- Wareham N.J. (Nicholas J.)
- Warren H. (Helen)
- Wessel J. (Jennifer)
- Willems S.M. (Sara)
- Willer C.J. (Cristen)
- Wilson J.F. (James)
- Winkler T.W. (Thomas W.)
- Witte D.R. (Deniel)
- Wood A.R. (Andrew)
- Woods M.O. (Michael)
- Wu Y. (Ying)
- Yaghootkar H. (Hanieh)
- Yao J. (Jiefen)
- Yao P. (Pang)
- Yerges-Armstrong L.M. (Laura)
- Young K.L. (Kristin L.)
- Young R. (Robin)
- Zeggini E. (Eleftheria)
- Zhan X. (Xiaowei)
- Zhang W. (Weihua)
- Zhao J.H. (Jing Hua)
- Zhao W. (Wei)
- Zheng H. (He)
- Zhou W. (Wei)
- Zwart J-A. (John-Anker)
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 09/02/2017
- Field of study
Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar Mohamed S.
- Abdel-Aziz Mahmoud
- Abdelrazik Marwa
- Abdollahi Hamed
- Abdullah T.
- Abecasis Goncalo
- Abedalthagafi M.
- Abel Lynn
- Abernathy C.
- Abraheem Azmeralde
- Abul-Husn Noura S.
- Acquilini D.
- Adams C.
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- Adams K.
- Adamsara Alireza
- Adanini Olurenke
- Adeleye O.
- Adra D.
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- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal Shruti
- Agüero D.
- Ahmad N.
- Ahmadi Saeideh
- Ahmed A.
- Ahmed Cecilia
- Akeroyd L.
- Akhtar M.N.
- Akinkugbe O.
- Aksentijevich Alexandra
- Al-Afghani H.
- Al-Awdah L.
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- Åsvold Bjørn Olav
- Publication venue
- Publication date
- 01/01/2022
- Field of study
Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease